rs2113628400

Variant names:

• chr6-7541920-G-A
• rs2113628400
• NM_004415.4:c.5G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-7541920-G-A
• chr6-7541920-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004415.4(DSP):​c.5G>A​(p.Ser2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DSP NM_004415.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DSP-AS1 (HGNC:56039): (DSP antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4	c.5G>A	p.Ser2Asn	missense_variant	Exon 1 of 24	ENST00000379802.8	NP_004406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.5G>A	p.Ser2Asn	missense_variant	Exon 1 of 24	1	NM_004415.4	ENSP00000369129.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.65	T;T
M_CAP	Pathogenic	0.78	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N;N
PhyloP100		2.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.16
Sift	Benign	0.11	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0010	B;.
Vest4		0.43
MutPred		0.098		Loss of glycosylation at S2 (P = 0.0601);Loss of glycosylation at S2 (P = 0.0601);
MVP		0.40
MPC		0.20
ClinPred		0.69	D
GERP RS		3.9
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.53
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2113628400; hg19: chr6-7542153;